Human leukocyte antigen Bw4 and Bw6 epitopes recognized by antibodies and natural killer cells

Lutz, Charles T.

doi:10.1097/mot.0000000000000103

Cited by 20 publications

(16 citation statements)

References 37 publications

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“…In addition, amino acids at positions 77, 80, 81, 82 and 83 have already been described to characterize the Bw4 and Bw6 motifs (Muller et al 1989 ). Bw4 specificity has been defined by the presence of N, D or S at residue 77 and IALR, TLLR or TALR amino acid motifs at residues 80–83(Lutz 2014 ). Since these motifs facilitate the distinction between serological subtypes, they were included in the analysis.…”

Section: Resultsmentioning

confidence: 99%

Specific amino acid patterns define split specificities of HLA-B15 antigens enabling conversion from DNA-based typing to serological equivalents

et al. 2020

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The HLA-B15 typing by serological approaches defined the serological subgroups (or splits) B62, B63, B75, B76, B77 and B70 (B71 and B72). The scarcity of sera with specific anti-HLA antibodies makes the serological typing method difficult to discriminate a high variety of HLA antigens, especially between the B15 antigen subgroups. Advancements in DNA-based technologies have led to a switch from serological typing to high-resolution DNA typing methods. DNA sequencing techniques assign B15 specificity to all alleles in the HLA-B*15 allele group, without distinction of the serological split equivalents. However, the presence of antibodies in the patient defined as split B15 antigens urges the identification of HLA-B*15 allele subtypes of the donor, since the presence of donor-specific antibodies is an important contraindication for organ transplantation. Although the HLA dictionary comprises information regarding the serological subtypes of HLA alleles, there are currently 394 B15 antigens out of 516 in the IPD-IMGT/HLA database (3.38.0) without any assigned serological subtype. In this regard, we aimed to identify specific amino acid patterns for each B*15 serological split, in order to facilitate the assignment of B*15 alleles to serological equivalents after high-resolution molecular typing. As a result, serological specificities of 372/394 not yet assigned alleles could be predicted based on amino acid motifs. Furthermore, two new serological types were identified and added, B62-Bw4 and B71-Bw4.

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Section: Resultsmentioning

confidence: 99%

Specific amino acid patterns define split specificities of HLA-B15 antigens enabling conversion from DNA-based typing to serological equivalents

et al. 2020

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“…Bw4 and Bw6 are mutually exclusive epitopes on the alpha 1 domain of HLA class I molecules (pos 77–83), Bw4 of which binds an array of diverse allotypes of immunoglobulin-like receptors of NK cells (KIR) in humans (Cella et al 1994 ; Gumperz et al 1995 , 1997 ; Lutz 2014 ). Since Bw4 and Bw6 epitopes are also known to be present on class I molecules in macaques, we searched for their presence/absence on class I molecules in the olive baboon.…”

Section: Resultsmentioning

confidence: 99%

MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

et al. 2018

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The olive baboon represents an important model system to study various aspects of human biology and health, including the origin and diversity of the major histocompatibility complex. After screening of a group of related animals for polymorphisms associated with a well-defined microsatellite marker, subsequent MHC class I typing of a selected population of 24 animals was performed on two distinct next-generation sequencing (NGS) platforms. A substantial number of 21 A and 80 B transcripts were discovered, about half of which had not been previously reported. Per animal, from one to four highly transcribed A alleles (majors) were observed, in addition to ones characterised by low transcripion levels (minors), such as members of the A*14 lineage. Furthermore, in one animal, up to 13 B alleles with differential transcription level profiles may be present. Based on segregation profiles, 16 Paan-AB haplotypes were defined. A haplotype encodes in general one or two major A and three to seven B transcripts, respectively. A further peculiarity is the presence of at least one copy of a B*02 lineage on nearly every haplotype, which indicates that B*02 represents a separate locus with probably a specialistic function. Haplotypes appear to be generated by recombination-like events, and the breakpoints map not only between the A and B regions but also within the B region itself. Therefore, the genetic makeup of the olive baboon MHC class I region appears to have been subject to a similar or even more complex expansion process than the one documented for macaque species.Electronic supplementary materialThe online version of this article (10.1007/s00251-018-1053-7) contains supplementary material, which is available to authorized users.

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“…Both HLA-B*38:68Q and HLA-B*38:01:01:01 express Bw4 epitope in α1-helix at position 77–83 24 , therefore anti-Bw4 antibody was used to detect the expression levels of HLA-B*38:68Q homozygous and HLA-B*38:68Q/B*38:01:01:01 heterozygous clones. The monoclonal anti-Bw4 antibody does not cross reactive to A66, C12 HLA antigens expressed on the HLA-B*38:01:01:01 homozygous TEM665 EBV B cell line using Luminex Single Antigen Bead (SAB) testing (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

Integrate CRISPR/Cas9 for protein expression of HLA-B*38:68Q via precise gene editing

Yin¹,

Reed²,

Zhang³

2019

Sci Rep

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The determination of null- or low-expressed HLA alleles is clinically relevant in both hematopoietic stem cell transplantation and solid organ transplantation. We studied the expression level of a questionable (Q) HLA-B*38:68Q allele, which carries a 9-nucleotide (nt) deletion at codon 230–232 in exon 4 of HLA-B*38:01:01:01 using CRISPR/Cas9 gene editing technology. CRISPR/Cas9 gene editing of HLA-B*38:01:01:01 homozygous EBV B cell line resulted in one HLA-B*38:68Q/B*38:01:01:01 heterozygous and one HLA-B*38:68Q homozygous clone. Flow cytometric analysis of monoclonal anti-Bw4 antibody showed the protein expression of HLA-B*38:01:01:01 in homozygous cells was 2.2 fold higher than HLA-B*38:68Q/B*38:01:01:01 heterozygous cells, and the expression of HLA-B*38:68Q/B*38:01:01:01 heterozygous cells was over 2.0 fold higher than HLA-B*38:68Q homozygous cells. The HLA-B*38:68Q expression was further confirmed using anti-B38 polyclonal antibody. Similarly, the expression of the HLA-B*38:01:01:01 homozygous cells was 1.5 fold higher than that of HLA-B*38:68Q/B*38:01:01:01 heterozygous cells, and the HLA-B*38:68Q/B*38:01:01:01 heterozygous cells was over 1.6 fold higher than that of HLA-B*38:68Q homozygous cells. The treatment of HLA-B*38:68Q homozygous cells with IFN-γ significantly increased its expression. In conclusion, we demonstrate that HLA-B*38:68Q is a low-expressing HLA allele. The CRISPR/Cas9 technology is a useful tool to induce precise gene editing in HLA genes to enable the characterization of HLA gene variants on expression and function.

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Human leukocyte antigen Bw4 and Bw6 epitopes recognized by antibodies and natural killer cells

Cited by 20 publications

References 37 publications

Specific amino acid patterns define split specificities of HLA-B15 antigens enabling conversion from DNA-based typing to serological equivalents

Specific amino acid patterns define split specificities of HLA-B15 antigens enabling conversion from DNA-based typing to serological equivalents

MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

Integrate CRISPR/Cas9 for protein expression of HLA-B*38:68Q via precise gene editing

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